title: Two different approaches to restore renal nitric oxide and prevent hypertension in young spontaneously hypertensive rats: l-citrulline and nitrate.
abstract: Nitric oxide (NO) deficiency mediates oxidative stress in the kidney and is involved in the development of hypertension. NO synthesis occurs via 2 pathways: nitric oxide synthase (NOS) dependent and NOS-independent. We tested whether the development of hypertension is prevented by restoration of NO by dietary l-citrulline or nitrate supplementation in young spontaneously hypertensive rats (SHRs). Male SHRs and normotensive Wistar Kyoto control rats (WKYs)s age 4 weeks were assigned to 4 groups: untreated SHRs and WKYs, and SHRs and WKYs that received 0.25% l-citrulline for 8 weeks. In our second series of studies, we replaced l-citrulline with 1 mmol/kg/d sodium nitrate. All rats were sacrificed at age 12 weeks. We found an increase in the blood pressure of SHRs was prevented by dietary supplementation of l-citrulline or nitrate. Both treatments restored NO bioavailability and reduced oxidative stress in SHR kidneys. l-Citrulline therapy reduced levels of l-arginine and asymmetric dimethylarginine (ADMA)-an endogenous inhibitor of NOS-and increased the l-arginine-to-ADMA ratio in SHR kidneys. Nitrate treatment reduced plasma levels of l-arginine and ADMA concurrently in SHRs. Our findings suggest that both NOS-dependent and -independent approaches in the prehypertensive stage toward augmentation of NO can prevent the development of hypertension in young SHRs.
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
authors.forename: Shao-Ju
authors.initials: SJ
authors.lastname: Chien
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
authors.forename: Kuan-Miao
authors.initials: KM
authors.lastname: Lin
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
authors.forename: Hsuan-Chang
authors.initials: HC
authors.lastname: Kuo
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
authors.forename: Chien-Fu
authors.initials: CF
authors.lastname: Huang
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
authors.forename: Ying-Jui
authors.initials: YJ
authors.lastname: Lin
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan; Department of Traditional Chinese Medicine, Chang Gung University, Linkow, Taiwan.
authors.forename: Li-Tung
authors.initials: LT
authors.lastname: Huang
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan; Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan. Electronic address: tainyl@hotmail.com.
authors.forename: You-Lin
authors.initials: YL
authors.lastname: Tain
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D002956:Citrulline / Q000008:administration & dosage*; D019587:Dietary Supplements; D006973:Hypertension / Q000517:prevention & control*; D008297:Male; D009566:Nitrates / Q000008:administration & dosage*; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
chemical_list: D009566:Nitrates; D002956:Citrulline; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; C031618:sodium nitrate; D001120:Arginine
keywords: 8-hydroxydeoxyguanosine; ADMA; ASL; ASS; BP; CAT; DDAH; EPR; IOD; NO; NOS; OHdG; ROS; SHR; WKY; Wistar Kyoto rat; argininosuccinate lyase; argininosuccinate synthetase; asymmetric dimethylarginine; blood pressure; cationic amino acid transporter; dimethylarginine dimethylaminohydrolase; eNOS; electron paramagnetic resonance; endothelial nitric oxide synthase; integrated optical density; nNOS; neuronal nitric oxide synthase; nitric oxide; nitric oxide synthase; reactive oxygen species; spontaneously hypertensive rat